Abstract
RationaleImpairment in time perception, a critical component of decision-making, represents a risk factor for psychiatric conditions including substance abuse. A therapeutic that ameliorates this impairment could be advantageous in the treatment of impulsivity and decision-making disorders.ObjectivesHere we hypothesize that the catechol-O-methyltransferase (COMT) inhibitor tolcapone, which increases dopamine tone in frontal cortex (Ceravolo et al Synapse 43:201–207, 2002), improves time perception, with predictive behavioral, genetic, and neurobiological components.MethodsSubjects (n = 66) completed a duration estimation task and other behavioral testing in each of two sessions after receiving a single oral dose of tolcapone (200 mg) or placebo in randomized, double-blind, counterbalanced, crossover fashion. Resting state fMRI data were obtained in a subset of subjects (n = 40). Subjects were also genotyped for the COMT (rs4680) polymorphism.ResultsTime perception was significantly improved across four proximal time points ranging from 5 to 60 s (T(524) = 2.04, p = 0.042). The degree of this improvement positively correlated with subjective measures of stress, depression, and alcohol consumption and was most robust in carriers of the COMT Val158 allele. Using seed regions defined by a previous meta-analysis (Wiener et al Neuroimage 49:1728–1740, 2010), we found not only that a connection from right inferior frontal gyrus (RIFG) to right putamen decreases in strength on tolcapone versus placebo (p < 0.05, corrected), but also that the strength of this decrease correlates inversely with the increase in duration estimation on tolcapone versus placebo (r = − 0.37, p = 0.02).ConclusionsCompressed time perception can be ameliorated by administration of tolcapone. Additional studies should be conducted to determine whether COMT inhibitors may be effective in treating decision-making disorders and addictive behaviors.
Highlights
IntroductionAs anyone who has ever taken a long car trip knows, individuals have different thresholds for deciding when to ask, BAre we there yet?^ many find it difficult to persevere in the face of unanticipated challenges—i.e., to continue despite obstacles and setbacks and to avoid making impulsive, disadvantageous decisions
Our subjective experience of time shapes our decision-making
We have previously demonstrated that the COMT inhibitor tolcapone reduces impulsive decision-making in a delay discounting paradigm (Kayser et al 2012)
Summary
As anyone who has ever taken a long car trip knows, individuals have different thresholds for deciding when to ask, BAre we there yet?^ many find it difficult to persevere in the face of unanticipated challenges—i.e., to continue despite obstacles and setbacks and to avoid making impulsive, disadvantageous decisions. This type of temporal impulsivity contributes to the propensity to develop problems with alcohol, drugs, gambling, overspending, and overeating (Hamilton et al 2015; London 2016) and to the deleterious behavioral consequences of neurodegenerative diseases such as frontotemporal dementia (Bertoux et al 2015). Expanding time horizon could potentially enable vulnerable individuals to wait longer for appropriate rewards and thereby improve many decision-making disorders
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